High and individual positive end-expiratory pressure (PEEP) during laparoscopic surgery may improve oxygenation and respiratory mechanics. We searched RCTs in PubMed, Cochrane Library, Web of Science, and Google Scholar from from from January 2000 to December 2023 comparing the different intraoperative PEEP (low PEEP (LPEEP): 0–5 mbar; moderate PEEP (MPEEP): 6–9 mbar; high PEEP (HPEEP): >=10 mbar; individualized PEEP (iPEEP): PEEP set by special physiological technique) on arterial oxygenation, respiratory compliance (Cdyn) or driving pressure, mean arterial pressure (MAP), and heart rate (HR) in patients during laparoscopic surgery in reverse Trendelenburg position. We calculated mean differences (MD) with 95% confidence intervals (CI), and predictive intervals (PI) using random-effects models. The Cochrane Bias Risk Assessment Tool was applied. 8 RCTs (n = 425) met the inclusion criteria. HPEEP vs. LPEEP increased PaO2/FiO2 (+ 129.93 [+ 75.20; +184.65] mmHg, p < 0.0001) with high variation of true effect (Chi2 34.92, p < 0.0001; I2 89%). iPEEP vs. LPEEP also increased PaO2/FiO2 + 130.23 [+ 57.18; +203.27] mmHg, p = 0.0005) with high variation of true effect (Chi2 26.95, p < 0.0001; I2 93%). HPEEP vs. LPEEP increased Cdyn (+ 15.06 [5.47; +24.65] ml/mbar, p = 0.002) with high variation of true effect (Chi2 93.16, p < 0.0001; I2 96%). iPEEP vs. LPEEP increased Cdyn (+ 22.46 [+ 8.56; +36.35] ml/mbar, p = 0.002) with high variability of the true effect (Chi2 53.92, p < 0.0001; I2 96%). HPEEP group had higher MAP as compared to LPEEP) + 4.36 [+ 0.36;+8.36], p = 0.03), variability of the true effect was nonsignificant. HR did nit differ between all comparisons. In patients with obesity undergoing surgery in the reverse Trendelenburg position HPEEP and iPEEP may improve oxygenation, decrease driving pressure, and increase dynamic compliance compared to LPEEP with high variation of true effect without relevant hemodynamic compromise. Data with MPEEP comparisons are inconclusive. CRD42023488971; registered December 14, 2023.

Введение.Саркомы составляют 1–2,5% всех злокачественных опухолей и характеризуются агрессивным ростом и высокой смертностью. Они могут возникать в различных органах, включая лицо. Лечение сарком включает хирургическое вмешательство, лучевую и химиотерапию. Радикальная резекция с сохранением функциональности и внешнего вида является приоритетным методом лечения. Цель исследования. Описать редкий клинический случай бифазной синовиальной саркомы щеки, диагностированной после неоднократных операций, и проанализировать эффективность хирургического лечения. Методы.Проведен анализ клинического случая пациента с рецидивирующей опухолью щеки, включающий клинико-рентгенологические, гистологические и иммуногистохимические исследования. Выполнена хирургическая резекция опухоли с пластикой дефекта. Результаты.Представлен вариант хирургического лечения синовиальной саркомы мягких тканей лица распространившейся в ретромаксиллярную и подвисочную области, с использованием челюстно-лицевого доступа по Лауэрс-Балону, позволяющий рассчитывать на радикальное удаление опухоли с сохранением более нормальных контуров лица. Гистологический анализ подтвердил диагноз бифазной синовиальной саркомы. Операция позволила удалить опухоль с сохранением кожных покровов. Послеоперационный период прошел без осложнений. Выводы.Дифференциальная диагностика сарком требует комплексного подхода. Радикальная резекция с последующей пластикой эффективна при лечении саркомы щеки, обеспечивая удовлетворительный функциональный и косметический результат. Introduction.Sarcomas account for 1–2.5% of all malignant tumors and are characterized by aggressive growth and high mortality. They can occur in various organs, including the face. Treatment of sarcomas includes surgery, radiation and chemotherapy. Radical resection with preservation of functionality and appearance is a priority treatment method. Objective. To describe a rare clinical case of biphasic synovial sarcoma of the cheek diagnosed after multiple surgeries and to analyze the effectiveness of surgical treatment. Methods. An analysis of the clinical case of a patient with a recurrent cheek tumor was performed, including clinical, radiological, histological and immunohistochemical studies. Surgical resection of the tumor with defect plastic surgery was performed. Results. A variant of surgical treatment of synovial sarcoma of facial soft tissues that has spread to the retromaxillary and infratemporal regions is presented, using the maxillofacial approach according to Lauers-Balon, which allows to count on radical removal of the tumor while preserving more normal facial contours. Histological analysis confirmed the diagnosis of biphasic synovial sarcoma. The operation allowed to remove the tumor while preserving the skin. The postoperative period passed without complications. Conclusions. Differential diagnostics of sarcomas requires a comprehensive approach. Radical resection with subsequent plastic surgery is effective in the treatment of cheek sarcoma, providing a satisfactory functional and cosmetic result. Кіріспе.Саркомалар барлық қатерлі ісіктердің1-2,5% құрайды және агрессивті өсумен және жоғары өліммен сипатталады. Олар әртүрлі органдарда, соныңішінде бетінде пайда болуы мүмкін. Саркоманы емдеу хирургияны, сәулеленуді жәнехимиотерапияны қамтиды. Функционалдылығы мен сыртқы түрін сақтайотырып, радикалды резекция емдеудің басым әдісіболып табылады. Зерттеудің мақсаты. Қайталанатын операциялардан кейін диагноз қойылған жақтың екі фазалы синовиальды саркомасының сирек кездесетін клиникалық жағдайынсипаттау жәнехирургиялықемніңтиімділігін талдау. Әдістері. Клиникалық, радиологиялық, гистологиялық және иммуногистохимиялық зерттеулерді қоса алғанда, бетінің қайталанатын ісігі бар науқастың клиникалық жағдайы талданды. Ақаудың пластикалықоперациясымен ісіктіңхирургиялықрезекциясы жасалды. Нәтижелер. Беттің жұмсақ тіндерінің...

Background: Central Asia is known to face various ecological challenges that constitute major risk factors for cancer. This study explored the cancer burden in Central Asia, where the estimates are among the highest worldwide. Methods: Extracting data from the latest global burden of disease study (GBD 2021), the authors investigated the disability-adjusted life years (DALYs), deaths, and incidence of various cancer groups in Central Asian countries from to 1990-2021. We conducted descriptive analyses of cancer statistics and calculated the average annual percent change (AAPC) to analyze the temporal patterns for individual country estimates. Results: Over the study period, DALYs decreased and were primarily driven by premature deaths, with pronounced estimates in male subjects. While DALYs, deaths, and incidence figures were somewhat comparable for most countries, Kazakhstan had exceptionally high estimates during the 1990s. However, over the following decades, the country revealed the highest decrease for all the metrics, measured by the AAPCs for incidence -1.32% (95% uncertainty interval [UI]: -1.44% to -1.19%); deaths -2.28% (95% UI: -2.51% to -2.05%); DALYs -2.50% (95% UI: -2.74% to -2.24%). Across the region, the leading cancer sites were tracheal, bronchus, and lung, stomach, colon and rectum and esophageal cancers, in both sexes combined. Sex-specific cancer estimates showed slight variations, with a notable burden observed in females. Conclusion: This study revealed an overall decrease in the cancer burden between 1990 and 2021. However, the temporal patterns of the risk factors remain a concern. Our findings highlight the importance of preventive measures and early diagnosis. Additionally, when interpreting GBD 2021 findings, future studies should consider the potential impact of salmon bias, where selective migration affects the modelled estimates.

Background.Multiple myeloma (MM) is a heterogeneous hematologic malignancy with variable clinical course and response to therapy [1,2]. Unfortunately, MM is still an incurable disease, and the difference in overallsurvival(OS) and progressive free surviva l (PFS) rates in patients varies depending on the risk group. Due to the limited access to high-tech molecular genetic studies for risk group stratification, it remains relevant to study more accessible prognostic markers, in particular based on flow cytometry data [1,8].Aim.In our study, our goal was to evaluate the level of CD56 expression on pathological plasma cells and their effect on the frequency of objective response to induction therapy and overall survival rates in patients with newly diagnosed MM.Materials and Methods.We conducted a retrospective single-center analysis of 26 newly diagnosed MM patients treated at the National Research Oncology Center in Astana, Kazakhstan. For immunophenotyping of plasma cells, we employed multicolor flow cytometry following the standardized EuroFlow protocol with its recommended antibody panels[7,17]. Only patients with ≥10% clonal plasma cells and an aberrant immunophenotype were included, in accordance with international recommendations [4,7,13]. Patients were stratified according to CD56 expression level. All patients received VCD induction therapy. Response was evaluated according to IMWG criteria, and OS was analyzed using Kaplan–Meier curves [3,11]. Results.High objective response rates and 100% overall survival at 24 months were observed in patients with CD56 expression ≤30%, while patients with negative CD56 expression and those with CD56 expression >30% were more likely to experience primary refractoriness and a tendency toward lower overall survival. However, in our study, the differences did not reach statistical significance (p=0.31), possibly due to the limited patient sample, but we do see a trend toward worse outcomes.Conclusion.CD56 expression is an accessible additional prognostic marker and may be used for treatment personalization in patients with multiple myeloma.Keywords:multiple myeloma, CD56, flow cytometry, immunophenotyping, prognosis.

Lentiviral vector (LV) production for CAR-T therapy remains challenging due to the limited scalability of adherent HEK293 cell cultures. To address this, we adapted HEK293FT cells directly to serum-free FreeStyle 293 Expression Medium, generating a novel suspension cell line, HEK293FT-DS. We characterized growth kinetics, stability over 35 passages, and transient transfection parameters (PEI:DNA ratio, cell density). The suspension-adapted cells grew with >93% viability and a specific growth rate of 0.54 day⁻¹, and maintained stable viable cell density (1.51 ± 0.03 × 10⁶ cells/mL) over 35 passages. The optimal PEI:DNA ratio was 2.5:1, and increasing the transfection cell density to 16 × 10⁶ cells/mL boosted functional titers to approximately 9 × 10⁶ TU/mL in clarified supernatant. Scaled production (1 L culture supernatant per batch) yielded up to 5 × 10⁹ TU. The resulting vectors efficiently transduced primary human T cells (57% CAR-positive cells) in a CliniMACS Prodigy-based process. The platform based on suspension-adapted HEK293FT-DS cells enables high-density transfection and provides a cost-effective, scalable alternative to commercial LV production systems, particularly suited for academic CAR-T cell manufacturing.

Introduction. Automated leukapheresis is the initial step in the production of CAR-T cell products and provides a concentrated fraction of mononuclear cells used for subsequent isolation, genetic modification, and expansion of T-lymphocytes. Despite the widespread introduction of CAR-T therapy into clinical practice, the questions of standardization of the leukapheresis procedure and assessment of the quality of the initial cellular material are still insufficiently investigated, especially in the organization of academic CAR-T cell production. Objective. To evaluate the quality of the mononuclear cell concentrate obtained by automated leukapheresis and determine the possibility of its use as the initial material for CAR-T cell production within the implementation of the national scientific and technical program of the Republic of Kazakhstan. Materials and methods. A pilot study was conducted at the Scientific and Production Center for Transfusiology. The study included 12 participants: 7 healthy donors and 5 patients with oncohematological diseases. Automated leukapheresis was performed using the Spectra Optia® system (Terumo BCT, USA) with the Mononuclear Cell Collection program. The technical success of the procedure, main technological parameters, cellular composition of the obtained product, number of viable CD45⁺/CD3⁺ T lymphocytes, and results of microbiological control were evaluated. Results. All automated leukapheresis procedures were completed in full without technical complications. The obtained mononuclear cell concentrates were suitable for subsequent CAR-T cell production. The mean volume of processed whole blood was 9549.5 mL, and the mean duration of the procedure was 230.8 min. The number of leukocytes in the obtained products ranged from 6.5×10⁹ to 32.1×10⁹ cells per dose, with a mean of 14.4±8.0×10⁹. The CD3⁺ T-lymphocyte content ranged from 129.1×10⁷ to 1629.7×10⁷ cells per dose, with a mean of 607.2±526.6×10⁷. Sterility of the cellular product was confirmed in all cases. Conclusion. The obtained results confirm the possibility of obtaining a mononuclear cell concentrate by automated leukapheresis that meets the requirements for subsequent CAR-T cell production. The developed algorithm for performing the procedure, laboratory quality assessment, and transfer of the cellular product can be used for further standardization of the collection of initial cellular material and development of a national platform for academic CAR-T cell production. Keywords: CAR-T cell therapy, automated leukapheresis, mononuclear cell concentrate, CD3⁺ T lymphocytes, cell therapy.